Production of n-acylated p-amino phenol



United States Patent Office 3,081,322 PRODUCTION OF N-ACYLATED P-AMINOPHENOL David W. Young, Homewood, Ill., assignor, by mesne assignments,to Sinclair Research, Inc., New York, N.Y., a corporation of Delaware NDrawing. Filed June 27, 1961, Ser. No. 119,841 4 Claims. (Cl. 260-404)larly the very low molecular weight members such as N- acetyl-p-aminophenol have also been found useful as a short stop in emulsionpolymerization systems, for example, the formation of GR-S rubbers,polybutadiene, polyisoprene, etc. and as an analgesic additive inaspirin.

The acyl p-amino phenols are generally prepared by a condensationreaction which comprises heating a monocarboxylic acid or its anhydridein the presence of an entraining solvent such as benzene, toluene,xylene and the like, with para amino phenol. The solid reaction productis then dehydrated by evaporation. The present invention follows thisgeneral method of preparing N- acylated p-amino phenols but is directedtoward the em ployment of novel catalysts for the condensation reaction.

One of the major problems with the above preparation is the color notedin the N-acylated p-amino phenol product. Whatever the cause, thiscoloration is particularly undesirable inasmuch as the N-acylatedp-amino phenols are widely used in clear, colorless materials such asresins, plastics and the like and as analgesic additives in aspirinswhich require a high degree of purity. Accordingly, to eliminate theundesirable color, various methods of recrystallization, distillationand solvent extraction have been employed with varying degrees ofsuccess. But even where successful in producing a pure product suchmethods are time consuming and costly. It has been proposed in Patent2,799,692 to Croxall et al. to

eliminate this undesirable color by carrying out the condensation of thereactants in accordance with the generally employed method utilizingboric acid as a catalyst but blanketing the reactants in an atmosphereof sulfur dioxide. Although this method produces a pure product, thebulk density of the final product leaves much to be desired.

It has now been found that light-colored N-acylated p-amino phenols canbe obtained by effecting the condensation of the p-amino phenol and amonocar-boxylic acid in the presence of certain boron-containing organiccompounds, preferably in an atmosphere of a non-oxidizing gas. Moreover,the products obtained by the method of the present invention can be ofhigh density. The advantages of a product of increased density are, ofcourse, that it lowers bulk and therefore reduces shipping costs; thatit makes available the use of more different and less expensive types offiltering devices and that it increases the filtration rate.

3,081,322 Patented Mar. 12, 1963 The boron containing organic compoundsemployed as a catalyst in the present invention can be illustrated bythe following general formulas:

wherein R is hydrogen or a monovalent hydrocarbon radical, includingsubstituted hydrocarbon radicals such as an oxygen-containing radical,e.g. ester radical, etc., of up to about 2 0 or 24 carbon atoms,preferably 1 to 6 carbon atoms, R is a divalent aliphatic hydrocarbonradical of up to 6 carbon atoms, preferably 2 to 4, and X is OR or R. Rcan be a straight or branch chained aliphatic, including cycloaliphatic,radical, an aryl group, e.g. phenyl, or a mixed alkyl-aryl radical butpreferably is an alkyl radical, and R and R can be substituted withnon-interfering groups. At least one of the R groups in the abovegeneral formulae is other than hydrogen. Examples of boron-containingorganic compounds that may be employed are the aryl boronic acids, alkylboric acids, trialkyl borates, trialkanol amine borates,trialkoxyboroximes, aryl dialkyl borates etc. The alkyl groups in thesecompounds preferably contain 1 to 6 carbon atoms. Suitable blanketingatmospheres for conducting the acylation of the present invention arenon-oxidizing gases such as carbon dioxide, sulfur dioxide, nitrogen,hydrogen, etc. The best results are obtained, however, when hydrogen isemployed as the blanketing atmosphere.

The catalysts of the present invention are employed in amountssuflicient to effect the N-aoylation, generally they are utilized incatalytic amounts of up to about 5 weight percent on the combined weightof the reactants and entraining solvents and preferably in an amount ofabout 1-2 weight percent. The reaction temperature is normally up toabout 200 C., preferably about to C.

In the practice of this invention, as in the prior art, themonocarboxylic acids having 2 to 21, preferably 12 to I18, carbon atomsare generally employed as the acid reactant. When the higher fatty acidscontaining upwards of 4 carbon atoms are used as the acid reactant, thecorresponding N-acylated p-amino phenols possess greater solubility andtherefore wider application as antioxidant additives in the variousorganic compositions that tend to gradually oxidize in storage. However,it will. be appreciated that the exact nature of the acyl substituentdoes not effect the condensation of the acid with the amine. Oxo-acidsand branched acids are less desirable from a reaction standpoint. Inselecting the p-amino phenol substituent either the unsubstitutedp-amino phenol 3 or the nuclear substituted p-amino phenols are suitablereactants within the scope of this invention as are the substitutedmonocarboxylic acids.

The following examples will illustrate the use of .the

4 mm.) and a maximum final temperature of 145 C. The residual melt wascooled slightly, and dissolved by adding 500 g. of 88% isopropanol. Thissolution was treated with 10 g. of activated powdered charcoal forboron-containing organic compounds of the present in- 5 2 /2 hours atreflux; and filtered while still hot. An vcntion as catalysts. Example Ibelow was run under atmosphere of S0 was maintained throughout theseopthe same conditions as given in Example I of Patent erations. Thecharcoal coke was washed twice with 44 No. 2,799,692 to Croxall et' al.All the results listed in g. portions of hot 100% isopropanol. Thefiltrate and Example I of the patent were checked with the resultswashings were transferred to" a clean two-liter resin flask of the runand were found to be accurate. For comand diluted with 200 ml. of hotwater. With agitation parison, the acylation was similarly conducted butin the and gradual cooling under a continuous atmosphere of absence of acatalyst. S0 the product was allowed to precipitate. At 58 C., thedropwise addition of 532 ml. of water was begun, be- EXAMPLE I ingcompleted in about one hour. Cooling was applied A two-liter reactionflask was equipped with an anchorby eans of an ice-bath, the temperatureof the mass type glass agitator, a Dean-Starke water trap carrying afalling to 15 C. condenser, a thermometer and a gas inlet tube for main-The supply of sulfur dioxide was then shut oil and the taming anatmosphere of S0 above the surface of the product collected on a 5-inchcentrifuge and washed with reaction mixture. The flask was charged with109 g. 50% by volume of cold aqueous isopropanol. The mal of pf P 200 ofcoconut fatty terial' was dried to constant weight in an oven at 60-75.ac d which was a mixture Of 10 Q12 14 and C16 fatty There was obtained242 g. (83.2% of theory based on acids laur c (C acid predominatmg (themixture havp-amino phenol), of a white powder having a melting rng anacid number of 246.0 and a molecular Weight of point of 124-125 C, Therun and density results are 228.0), 72 g. of toluene and 3.8 g. ofpowdered boric h w in Table I below. acid catalyst. The leg of theDean-Starke trap was filled with 20 ml. of toluene and heating andagitation were EXAMPLE H started. A slow stream of sulfur dioxide waspassed over Example I above was conducted employing as catalysts thesurface of the reactants. The charge was heated at the boron-containingorganic compounds identified in 135-140 C., water being removed fairlyrapidly at the Table I below and the blanketing atmosphere alsoindibeginning and more slowly as the reaction proceeded. A cated inTable I. The reaction rates and certain density total of 18.5 ml. ofwater was collected in six hours. determinations are shown in Table Ibelow. In each case The toluene was distilled at reduced pressure (15-20a white product was obtained.

T able I H2O eliminated at reaction time of- Catalyst Catalyst Inert211511105. Density, weight g./100 cc.

(g.) 2 hrs 3 hrs. 4 hrs. 5 hrs. 6 hrs.

None 0. 0 2. 5 4. 6.5 7. 75 8.5 H3130: (Ex. I): 3.8 so. 18.5 20.0Benzene boromc ac 3.8 Nitr0gen. 7.0 11.5 14.0 15.5 16.75

Nonylboric acid 3.8 do 6.0 9.0 10.5 12.0 13.5 as do 8.0 10.5 12.5 14.014.5 OH

Co 19B Tribenzylborate 3.8 Hydrogen 6.5to 7.0 11.5 13.25 .150

Trimethoxyboroxime 3.8 do 8.0 13. 25 14.5 15.5

CHsO-B B-OCHa l OOH:

Tricthanolamine borate 3.8 -.-.do. 3.0 5.5 8.0 9.5 10.5 43.5

CHgCHgO NCHiCH;O-B

OHT-OHFO 2,6-di-tert-butyl-4-111ethyl-phenyl-di-n-butyl borate 3.8 do5.5 9.5 11.5 12.5 13.5

See footnotes at end of table.

Table l-Continued H eliminated at reaction time of Catalyst CatalystInert atmos. Density, weight gJlOO cc.

(g.) 2 hrs. 3 hrs. 4 hrs. 5 hrs. 6 hrs.

l O-C4H9 OHs- OB\ O C 4H0 H:)s Tri-n-butylbor 3. 8 Nitrogen 9. 0 13. 716. 0 16. 7 17.0

3. 8 Hydrogen.-- 7. 0 10. 5 13. 0 14. 2 14. 5 I 44. 8 3. 8 Nitr0gen..8.0 12. 0 14. 0 15. 0 15. 5

O C 4H9 O C 4H9 0--C4Hn Tris-[3-2,2,4-trimethyl-pentyl-iso-butyrate)]borate 3. 8 Hydrogen. 9 10. 5 12. 3 13. 4 13. 8 2 38 1 Sublimed readilyfrom reaction mixture, during reaction, reducing catalyst in vessel.

2 Recrystallized from isopropanol.

Examination of Table I clearly shows the effectiveness of theboron-containing organic compounds of the present invention as catalystsin the N-acylation of p-amino phenol. Also shown is the product densityadvantages obtained by employing the catalysts of the present invention.All density determinations were made by first tapping the sample vesselseveral times.

It is claimed:

'1. In a method for the production of N-acylated pamino phenol bycondensing p-arnino phenol with a monocarboxylic acid of 2-21 carbonatoms, the improvement which comprises conducting the reaction in thepresence of a catalytic amount of a boron-containing organic compoundselected from the group consisting of RO wherein R is selected from thegroup consisting of hydrogen and a monovalent hydrocarbon radical of upto arbon atoms, R is a divalent aliphatic hydrocarbon radical of up to 6carbon atoms and X is selected from the group consisting of -OR and Rand at least one R in the formulae is a monovalent hydrocarbon radicalof up to 20 carbon atoms.

2. The method of claim 1 wherein R is a monovalent hydrocarbon radicalof 1 to 6 carbon atoms.

3. In a method for the production of N-acylated pamino phenol bycondensing p-amino phenol with a monocarboxylic acid of 2 to 21 carbonatoms, the improvement which comprises conducting the reaction in thepresence of a catalytic amount of a boron-containing organic compoundselected from the group consisting of References Cited in the file ofthis patent UNITED STATES PATENTS Garbo Aug. 12, 1952 Cottle et a1 Feb.4, 1958 Schulze Aug. 4, 1959

1. IN A METHOD FOR THE PRODUCTION OF N-ACYLATED PAMINO PHENOL BYCONDENSING P-AMINO PHENOL WITH A MONOCARBOXYLIC ACID OF 2-21 CARBONATOMS, THE IMPROVEMENT WHICH COMPRISES CONDUCTING THE REACTION IN THEPRESENCE OF A CATALYTIC AMOUNT OF A BORON-CONTAINING ORGANIC COMPOUNDSELECTED FROM THE GROUP CONSISTING OF